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Background: Drugs Targeting The Renin System May Not Be Clinically Equivalent

Presentation: Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRI) for Adults With Hypertension
Keywords: renin system | ACEIs | ARBs | angiotensin II | DRI | aliskiren
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Evidence on Adverse Effects

Presentation: Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRI) for Adults With Hypertension
Keywords: adverse effects | cough | persistence | withdrawals
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Gaps in Knowledge

Presentation: Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), or Direct Renin Inhibitors (DRI) for Adults With Hypertension
Keywords: gaps in knowledge | future research | subgroups | clinical trials
This slide summarizes the most pertinent results from the Comparative Effectiveness Review (CER) on the benefits and harms of adding an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to standard medical therapy for stable ischemic heart disease with preserved left ventricular systolic function as compared to standard medical therapy alone or with a placebo. The next several slides will discuss these data in greater detail. When considered together, the benefits and harms of adding an ACEI or an ARB to standard medical therapy indicate that there may be a clinical benefit from such therapy for some patients with stable ischemic heart disease and preserved left ventricular systolic function (LVSF). However, the potential risks of cough, syncope, or hyperkalemia should be considered for each individual patient before adding an ACEI or an ARB to his or her treatment regimen. Very few of the trials evaluated for the CER compared the addition of an ACEI or an ARB or both to an active control. Only two trials compared the addition of an ACEI or a calcium channel blocker to standard medical therapy (Nissen et al., 2004; Yiu et al., 2004). In both trials, the clinical benefits were similar between the two treatment arms, and there was some limited evidence that ACEIs may increase the risk for hypotension and cough. Additional trials are required to make any definitive clinical recommendations with regard to the addition of calcium channel blockers over ACEIs to standard medical therapy. Cardiovascular events are the leading cause of death in patients treated with hemodialysis for chronic kidney disease. Among these patients, left ventricular hypertrophy is considered to be an ischemic heart disease equivalent, as defined by the National Kidney Foundation. In a clinical trial conducted by Zannad et al. (2006), however, there was no impact on cardiovascular mortality after fosinopril, an ACEI, was added to standard therapy for patients with end-stage renal disease and left ventricular hypertrophy.
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Results of Trials Evaluating the Addition of an ACEI or an ARB to Standard Therapy for Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function
Keywords: angiotensin II-receptor blocker | benefit | cough | hyperkalemia | renal disease | stable ischemic heart disease | syncope | angiotensin-converting enzyme inhibitor
This slide summarizes the detailed evidence from the Comparative Effectiveness Review (CER) with regard to combination therapy with an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB). In the only trial available for analysis, the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET; Yusuf et al., 2008), an ACEI/ARB combination (ramipril + telmisartan) was added to standard medical therapy for patients with stable ischemic heart disease (IHD) and a preserved left ventricular systolic function (LVSF) and compared to the addition of only an ACEI (ramipril). ONTARGET also compared ramipril to telmisartan (ARB); this, however, was not part of the analysis of this CER and will not be discussed in this slide.Based on the analysis of this single trial, the CER found no evidence that adding an ACEI/ARB combination to standard therapy provides any additional clinical benefit to patients with stable IHD and preserved LVSF when compared to adding an ACEI alone with regard to total mortality, cardiovascular mortality, fatal + nonfatal myocardial infarction, fatal + nonfatal stroke, the composite risk of the previous three outcomes, new atrial fibrillation, worsening or new angina, hospitalizations for angina, heart failure-related hospitalizations, or revascularizations. The level of evidence for these findings was deemed to be moderate. However, there also is a moderate level of evidence that there is an increased risk for the adverse events listed in this slide when ACEIs and ARBs are combined. The incidences of cough and angioedema did not reach statistical significance between the two treatment groups. The incidences of rash and blood dyscrasias were not reported in the original trial report.
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Overall Summary of the Evidence-Based Benefits and Harms of Adding an ACEI/ARB Combination Versus an ACEI Alone to Standard Medical Therapy for Stable Ischemic Heart Disease With Preserved Left Ventricular Systolic Function

Presentation: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and/or Angiotensin II Receptor Blockers Added to Standard Medical Therapy for Treating Patients With Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function
Keywords: angiotensin II-receptor blocker | benefits | combination therapy | harms | stable ischemic heart disease | angiotensin-converting enzyme inhibitor
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Background: Additional Issues

Presentation: Comparative Effectiveness of Management Strategies for Adults With Gastroesophageal Reflux Disease: An Update
Keywords: clopidogrel | cotherapy | extraesophageal | omeprazole | Prilosec | refractory | diagnosis
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Findings of the Comparative Effectiveness Review: Medication (2 of 3)

Presentation: Comparative Effectiveness of Management Strategies for Adults With Gastroesophageal Reflux Disease: An Update
Keywords: GERD | histamine type 2 receptor antagonist | H2RA | proton pump inhibitor | PPI | extraesophageal
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Findings of the Comparative Effectiveness Review: Surgery (2 of 3)

Presentation: Comparative Effectiveness of Management Strategies for Adults With Gastroesophageal Reflux Disease: An Update
Keywords: fundoplication | surgery | GERD
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Knowledge Gaps and Future Research Needs

Presentation: Comparative Effectiveness of Management Strategies for Adults With Gastroesophageal Reflux Disease: An Update
Keywords: knowledge gaps | future research needs | insufficient evidence | GERD | behavioral modifications | extraesophageal | refractory symptoms
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Adverse Events of Treatment

Presentation: Management of Chronic Kidney Disease Stages 1–3
Keywords: chronic kidney disease | adverse effects | treatment | withdrawal | hypotension | cough | edema | hyperkalemia
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Conclusions: Treatment (2 of 2)

Presentation: Management of Chronic Kidney Disease Stages 1–3
Keywords: ACEI | adverse events | ARB | conclusions | outcomes | statin | chronic kidney disease
Patient Discussion: Potential Harms of ACEIs You then discuss the possible risks of adverse effects from taking an ACEI, so that the patient can weigh the benefits and harms with you to determine an appropriate decision. You explain that research has found that he may experience: A. Nothing. B. Hypotension. C. Hypertension. D. Need for future revascularizations. E. Syncope, cough, and hyperkalemia.
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Patient Discussion: Potential Harms of ACEIs

Presentation: Management of the Patient with Stable Ischemic Heart Disease and Preserved Left Ventricular Systolic Function
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